A paradox resolved: the postprandial model of insulin resistance explains why gynoid adiposity appears to be...

Although an increased visceral adipose mass is clearly linked to insulin resistance syndrome and increased vascular risk, some studies suggest that the ratio of visceral to subcutaneous fat (gynoid or abdominal) is a better correlate of insulin resistance. For example, the utility of waist-to-hip ratio as a risk factor illustrates this principle--and suggests that gynoid obesity may somehow be protective. The postprandial model of insulin resistance--the hypothesis that excessive postprandial free, fatty acid (FFA) flux plays a key role in the genesis of the insulin resistance syndrome--may help to rationalize this seemingly paradoxical observation. A high proportion of this FFA flux is derived, not from adipocytes, but from meal-derived fatty acids that adipocytes fail to store following chylomicron breakdown; insulin-resistant adipocytes are notably inefficient in regard to FFA storage. Hypertrophied visceral adipocytes are poorly insulin sensitive, whereas gynoid adipocytes tend to be highly insulin sensitive. After a fatty meal, the lipoprotein lipase (LPL) activities associated with the various depots--visceral and subcutaneous adipocytes, as well as skeletal muscle--effectively compete to hydrolyze chylomicra. When circulating triglycerides are broken down by muscle or by insulin-sensitive subcutaneous adipocytes, the evolved fatty acids are apt to be stored immediately--whereas the fatty acids produced by chylomicron breakdown in the visceral depot are much more prone to escape to the circulation and contribute to high postprandial FFA flux. Thus, the LPL activity of gynoid adipocytes provides protection from the potentially adverse metabolic consequences of fatty meals--and a large mass of gynoid adipocytes presumably is a marker for high LPL activity in this depot. The ability of the postprandial model of insulin resistance to rationalize the seeming protection afforded by gynoid obesity constitutes evidence that this model has validity.